We propose to conduct a randomized, double-blind, placebo-controlled, 2x2 factorial trial of beta-carotene and vitamin E as chemoprophylactic agents in reducing the incidence of lung cancer among women at high risk due to their long duration of cigarette smoking. Due to the design, we can also independently assess the potential chemopreventive role of these two micronutrients on incidence of breast cancer. This trial will be conducted among approximately 19,000 female U.S. nurses, 40-74 years of age, with a total current or past duration of cigarette smoking of at least 15 years. We will send a description of the trial and questionnaires inquiring about past medical history, diet, risk factors for cancer, and possible contraindications to beta-carotene and vitamin E to approximately 1.3 million potential participants. The nurses who agree to participate will be sent calendar packs containing placebos for a three-month "run-in" period. This strategy will serve to exclude poor compliers, thus increasing the power of the trial to detect small to moderate effects. Participants who comply with the treatment regimen and the trial guidelines during the run-in period and who remain willing and eligible, will be assigned at random to receiving either beta-carotene (50 mg q.o.d.) or placebo. To maintain high compliance, pills will be packaged in convenient, one-month calendar packs, so that each participant will take only one pill per day. At six-month intervals we will mail calendar packs and questionnaires asking about compliance, the occurrence of any side effects, and the incidence of endpoints. Endpoints will be confirmed by review of medical records. Based upon our successful experience with the ongoing Physicians Health Study, the demonstrated high compliance and follow-up of the sample of nurses who participated in our recently completed two-year pilot study, as well as the long-term experience from our large cohort study of nurses, we believe this trial will provide definitive tests of each of these two micronutrients in the primary prevention of the two leading types of cancer among middle-aged and older women.